Takeda Canada released the news results from its Phase 3b clinical trial, VARSITY, comparing Takeda’s ENTYVIO® (vedolizumab) to AbbVie’s HUMIRA® (adalimumab) in patients with moderately-to-severely active ulcerative colitis (UC) who had failed conventional treatments showed the superiority of ENTYVIO®. The data were presented at the European Crohn’s and Colitis Organization (ECCO) Congress in Copenhagen.
Takeda reported today the VARSITY trial is the first completed direct comparison of biological agents in inflammatory bowel disease. The sponsor recruited 330 research sites in 37 countries. They ultimately successfully recruited 769 patients.
The primary endpoint, significantly better rates of clinical remission, was met during the 52-week treatment span. Patients treated with ENTYVIO also met the key secondary endpoint—demonstrating significantly better rates of mucosal healing.
Takeda reported that 31.3%(n=120/383) of patients receiving ENTYVIO® intravenous (IV) achieved the primary endpoint of clinical remission compared to 22.5% (n=87/386) of patients treated with Humira® subcutaneous (SC) at week 52, with the difference being statistically significant (p=0.0061). Furthermore, treatment with ENTYVIO® was associated with statistically significant higher rates of mucosal healing at week 52, with 39.7% of patients receiving ENTYVIO® achieving mucosal healing compared to 27.7% treated with Humira® (p=0.0005). A non-statistically significant difference in favor of Humira® was seen in the percentage of patients using oral corticosteroids at baseline who discontinued corticosteroids and were in clinical remission at week 52.
”VARSITY is important because is it the first IBD study to compare biologics treatments head to head and also because it has the potential to change clinical practice for the future. Achieving mucosal healing and clinical remission are important criteria in treatment selection and these results are a good indicator that for certain patients with moderate to severely active ulcerative colitis vedolizumab can be used as first line biologic treatment.”
The FDA and EMA have approved ENTYVIO in May 2014 followed by Canada a couple years later.
This news brings hope to those struggling with moderately to severely active ulcerative colitis (irritable bowel disease) who have failed conventional treatments may have another option in the future. A brief review of Ulcerative Colitis (UC) medication treatments.
Many patients with UC are prescribed 5-ASAs that are supposed to calm inflammation in the gut. This class of treatment includes:
- Balsalazide (Colazal)
- Mesalamine (Ascol HD, Delzicol)
- Olsalazine (Dipentum)
- Sulfasalazine (Azulfidine)
These drugs can be taken by mouth or as an enema or suppository—depending on how the colon may be affected. These may be adequate if UC is in mild to moderate stage. If these medicines don’t work, other treatments (including surgery) are considered including a class popularly known as “steroids.” For example in significant flare-ups, physicians may prescribe corticosteroids (referred to as budesonide, hydrocortisone, methylprednisolone or prednisone). These drugs suppress the immune system in an attempt to help the body overcome inflammation. They can be taken via pill, IV, enema or suppositories. Because the steroids impact the immune system they are not a long-term solution for UC. Material side effects can occur.
For moderate to severe UC cases, physicians may consider immunomodulators if 5-ASAs and steroids are not working. The most common treatments for UC in this class include:
- Azathioprine (Azasan, Imuran)
- Mercaptopurine (Purinethol, Purixan)
- Cyclosporine (Gengraf, Neoral & Sandimmune)
These powerful treatments come with the risk of significant side effects and hence are typically not used unless other treatments are not working.
Biologics are increasingly an option and ENTYVIO falls in this category. Biologic drugs are designed and developed to target specific immune system targets. For example, they can isolate tumor necrosis factor (TNF) which has been established as a cause of inflammation. They can be called “Anti-TNF drugs.” Approved Anti-TNFs include:
Adalimumab (HUMIRA): Made by AbbVie this has become one of the world’s top selling drugs. It is often prescribed for UC. Because of an intertwining intellectual property rights (memorialized in patents) AbbVie has little biosimilar competition until 2023. Biosimilar competition is more robust in Europe. Biosimilars to HUMIRA include CYLTEZO which was approved by the FDA in 2017. TrialSite News recently wrote about the Boehringer Ingelheim gutsy move take on AbbVie’s patent thicket in the United States. At stake—4 years of market revenue for AbbVie’s HUMIRA. AMJEVITA which was a biosimilar to HUMIRA produced by American biotech giant Amgen. In 2017, Amgen negotiated a deal with AbbVie to postpone the launch: they would not enter the market in the Europe till 2018 and the United States in 2023. Economic laws of supply and demand are shaped by powerful business interests—AbbVie secured greater market share and avoided price pressures creating a windfall for the Chicagoland giant.
Golimuab (SIMPONI) is a human monoclonal antibody used as an immunosuppressive drug and known as SIMPONI. Developed by conglomerate Johnson & Johnson, it was approved for UC in both Europe and the U.S. in 2013. A TNF inhibitor, it was approved for UC in 2013. Another biologic is Johnson & Johnson’s REMICADE and biosimilars from Merck RENFLEXIS and INFLECTRA manufactured by South Korea-based Celltrion. And of course there is Takeda’s ENTYVIO and the most recent results from the VARSITY study.
There are critics of vedolizumab. For example, James Lord, MD, PhD, of the Benaroya Research Institute Virginia Mason Medical Center presented controversy: Vedolizumab Should not be Used as a First Line Biologic in IBD. Dr. Lord concludes “first line therapy for UC or Crohn’s should be a combination therapy with anti-TNF + thiopurine, if possible: if thiopurine-intolerant or obese, vedolizumab and anti-TNF therapy are comparable for UC.” He concludes vedolizumab is inferior to anti-TNF monotherapy for Crohn’s.